USC Researchers Link Genetic Marker To Rectal Cancer Treatment

Photo: Heinz-Josef Lenz, M.D., professor of medicine and preventive medicine in the division of medical oncology at the Keck School of Medicine of USC

A team
of researchers led by Keck School of Medicine of the University of
Southern California (USC) oncologist Heinz-Josef Lenz,
M.D.,
has identified a genetic marker that may predict which patients with
rectal cancer can be cured by certain chemotherapies when combined with
surgery. The discovery, scheduled for publication in the August 1
edition of Clinical
Cancer Research, brings doctors closer to customizing cancer
treatment to individual patients.

Lenz, professor of medicine and preventive medicine in the division of
medical oncology at the Keck School and the study’s principal
investigator, analyzed the DNA of European patients with locally
advanced rectal cancer who were treated with cetuximab (marketed as
Erbitux) prior to surgery.
“Cetuximab is usually used for metastatic colon cancer, for which it is
effective. We’re asking if it could be effective for locally advanced
rectal cancer,” said Lenz, associate director of the Gastrointestinal
Oncology Program at the USC Norris
Comprehensive Cancer Center and Hospital.

Colorectal cancer is the third most commonly diagnosed cancer and the
third leading cause of cancer death among men and women in the United
States, according to the American Cancer Society. The disease develops
in the colon or rectum and, if detected in its early stages, usually
can be completely removed by surgery. When it is locally advanced,
however, the tumor cannot be easily removed and doctors prescribe
chemotherapy and radiation to make it more manageable before attempting
surgical removal.

The retrospective analysis, first published online on June 14, found
that 45 percent of patients with a particular genetic combination (EGF
61 G/G) emerged disease-free when treated with cetuximab before
surgery, compared to 21 percent and 2 percent of patient groups who did
not have the same genotype. This is the first study to suggest that the
genetic variation — detectable by blood test — can be used to predict
whether a patient with locally advanced rectal cancer will respond to
cetuximab before surgery.

Cetuximab is a drug that is typically used to treat head and neck
cancer and colorectal cancer that has spread to other parts of the
body. It blocks epidermal growth factor receptors (EGFR) from binding
with epidermal growth factor (EGF) proteins found in the body, which
have been linked to increased risk for cancer. For tumors that are
difficult to cut out but have not yet spread to other parts of the
body, the standard treatment is a combination of capecitabine (Xeloda),
fluorouracil (5-FU) and radiation. The patients in the study received
intravenous doses of cetuximab in addition to standard care.

Additional data is required to validate the results, Lenz said. His lab
is participating in another trial looking at a larger sample size in
the United States.

The study was performed in the Sharon A. Carpenter Laboratory at the
USC Norris Comprehensive Cancer Center and Hospital and funded by the
National Institutes of Health, Dhont Family Foundation, Deutsche
Forschungsgemeinschfat (DFG), Cologne Fortune and San Pedro Peninsula
Cancer Guild. It is the second study published in Clinical Cancer
Research that uses the same data set; the first measured gene
expression levels of proteins involved in tumor growth. Co-authors
include Siwen Hu-Lieskovan, Wu Zhang, Dongyun Yang, Alexander Pohl and
Melissa Labonte, among others.